glycolysis

What does glycolysis convert glucose into?

2 pyruvate; via 2 phosphorylated oxidations + 1 oxidation reaction

What happens to excess glucose in glycolysis in the liver?

Converted into fatty acids for storage (glycogen)

5 key enzymes of glycolysis

1. Hexokinase / Glucokinase 2. PFK-1 and PFK-2 3. G3P dehydrogenase 4. 3-Phosphoglycerate kinase 5. Pyruvate kinase

Irreversible enzymes of glycolysis

1. Hexokinase / Glucokinase 2. PFK-1 3. Pyruvate kinase

ATP yield of glycolysis in erythrocytes (RBCs)

2 ATP (anaerobic)

What do kinases do?

Attach a phosphate group from ATP to a substrate

Hexokinase vs. glucokinase — shared function

Both convert glucose → glucose-6-phosphate

Hexokinase — location and regulation

Found in most tissues; inhibited by its own product, glucose-6-phosphate (product inhibition)

Glucokinase — location and regulation

Found in liver and pancreatic beta cells; induced (upregulated) by insulin

Hexokinase Km

Low Km — reaches maximum velocity even at low glucose concentrations (high affinity)

Glucokinase Km

High Km — activity increases proportionally with glucose concentration (acts as a glucose sensor)

Glucose-6-phosphate → next step

Converted to fructose-6-phosphate by an isomerase

PFK-1 reaction

Phosphorylates fructose-6-phosphate → fructose-1,6-bisphosphate (irreversible, rate-limiting step)

PFK-1 inhibitors

ATP and citrate — signals that the cell already has enough energy, so glycolysis should slow down

PFK-1 activator

AMP — signals low energy state, so glycolysis should speed up

What activates PFK-2? What does it do?

Insulin activates PFK-2 → converts F6P to fructose-2,6-bisphosphate → activates PFK-1 → increases glycolysis

What deactivates PFK-2? What does it do?

Glucagon deactivates PFK-2 → lowers fructose-2,6-bisphosphate → inhibits PFK-1 → slows glycolysis

G3P dehydrogenase reaction

Converts G3P (glyceraldehyde-3-phosphate) → 1,3-bisphosphoglycerate; adds inorganic phosphate and reduces NAD⁺ to NADH

3-Phosphoglycerate kinase reaction

Transfers phosphate from 1,3-bisphosphoglycerate to ADP → produces ATP (substrate-level phosphorylation) and 3-phosphoglycerate

Substrate-level phosphorylation

ADP is directly phosphorylated to ATP by transfer from a high-energy substrate (contrast with oxidative phosphorylation)

Pyruvate kinase reaction

Converts PEP (phosphoenolpyruvate) → pyruvate via substrate-level phosphorylation (ADP → ATP); irreversible

Pyruvate kinase activator

Fructose-1,6-bisphosphate (product of PFK-1 reaction)

Feed-forward activation

A product of an earlier reaction in a pathway activates a later enzyme in the same pathway — e.g., F-1,6-BP activating pyruvate kinase

Fermentation — definition and key enzyme

Occurs in the absence of oxygen; lactate dehydrogenase oxidizes NADH → NAD⁺ to keep glycolysis running

Why is fermentation necessary?

Without mitochondria or oxygen, available NAD⁺ gets used up (reduced to NADH), halting glycolysis; fermentation regenerates NAD⁺

Lactate dehydrogenase reaction

Reduces pyruvate (3C) → lactate (3C) while oxidizing NADH → NAD⁺

Yeast fermentation

Converts pyruvate → ethanol + CO₂; also replenishes NAD⁺

3 important glycolysis intermediates

1. DHAP (dihydroxyacetone phosphate) 2. 1,3-Bisphosphoglycerate (1,3-BPG) 3. PEP (phosphoenolpyruvate)

DHAP

Formed from fructose-1,6-bisphosphate; can be isomerized to G3P, which can be converted into glycerol

1,3-BPG and PEP

High-energy intermediates used to generate ATP via substrate-level phosphorylation

Biphosphoglycerate mutase (RBCs)

Converts 1,3-BPG → 2,3-BPG; a mutase moves a functional group (here, phosphate) within the same molecule

2,3-BPG function

Binds allosterically to hemoglobin A, decreasing its affinity for oxygen — promotes O₂ release to tissues

Why doesn't 2,3-BPG bind fetal hemoglobin (HbF) well?

HbF has a naturally higher affinity for oxygen than HbA, which allows it to preferentially capture oxygen from maternal blood; 2,3-BPG binding would interfere with thi